• Title/Summary/Keyword: EMT

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Transforming Growth Factor-β-Induced RBFOX3 Inhibition Promotes Epithelial-Mesenchymal Transition of Lung Cancer Cells

  • Kim, Yong-Eun;Kim, Jong Ok;Park, Ki-Sun;Won, Minho;Kim, Kyoon Eon;Kim, Kee K.
    • Molecules and Cells
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    • v.39 no.8
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    • pp.625-630
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    • 2016
  • The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-${\beta}1$ treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-${\beta}1$-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-${\beta}$-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.

Prehospital Care of 119 EMT for Non-traumatic Cardiac Arrest and Improvement to Increase Advanced Care Rate (119 구급대원의 비외상성 심정지 환자의 병원전 처치실태 및 전문 처치율 향상을 위한 개선 방안)

  • Lee, Kyoung-Youl;Yun, Seong-Woo
    • Fire Science and Engineering
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    • v.25 no.5
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    • pp.21-31
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    • 2011
  • This study aimed at evaluating and developing 119 emergency medical technicians' prehospital care for non-traumatic cardiac arrest. Total 322 EMT in Chungnam province and Daejeon city filled out the self-administered questionnaire. The data were analyzed by SPSS 18.0 for descriptive statistics. Among the 322 EMT, 309 (97%) and 169(53%) always or almost performed CPR and AED for nontraumatic cardiac arrest patient, respectively. Among the advanced EMT and nurse, IV were sometimes or not performed at 94.7% and medication including epinephrine which commonly used for survival of cardiac arrest were treated just at 9.3 % (14 person). The reason they did not perform each procedure for airway management, AED or IV was lack of manpower, limit of time or joggle of ambulance and legal restrictions. In conclusion, to increase survival rate of non-traumatic cardiac arrest in out-of-hospital, it is necessary to increase manpower, legal protection of EMS, establishment of standard operating procedure, practice for improvement technique and use of medication for ACLS.

Epithelial-mesenchymal Transition is Associated with Acquired Resistance to 5-Fluorocuracil in HT-29 Colon Cancer Cells

  • Kim, A-Young;Kwak, Jae-Hwan;Je, Nam Kyung;Lee, Yun-hee;Jung, Young-Suk
    • Toxicological Research
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    • v.31 no.2
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    • pp.151-156
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    • 2015
  • 5-Fluorouracil (5-FU) is commonly used for the therapy of colon cancer; however, acquired resistance to 5-FU is a critical barrier to successful treatment and the primary cause of chemotherapy failure. Epithelial-mesenchymal transition (EMT) is a process whereby cells undergo alterations in morphology and molecular characteristics promoting tumor progression and metastasis. Accumulating evidence shows that transition from epithelial to mesenchymal phenotype in cancer cells is associated with their resistance to chemotherapy. However, it is still poorly understood whether EMT is involved in acquired resistance to 5-FU. In this study, we developed an in vitro cell model, 5-FU-resistant HT-29 colon cancer cells, and characterized the differences in cellular morphology and molecular alterations between parental and resistant cells. In accord with mesenchymal-like morphology of 5-FU-resistant HT-29 cells, the expression of the mesenchymal marker fibronectin was significantly increased in these cells in comparision with that in the parental cells. Of interest, we also found a marked increase in the expression of EMT-inducing transcription factors Twist, Zeb1, and Zeb2. Finally, 5-FU-resistant cells showed enhanced migration in comparison with parental HT-29. Taken together, these results indicate that EMT could be associated with 5-FU resistance acquired by HT-29 cells. A specific role of each transcription factor found in this study will require further investigation.

The Epithelial-Mesenchymal Transition During Tooth Root Development

  • Kang, Jee-Hae;Park, Jin-Ho;Moon, Yeon-Hee;Moon, Jung-Sun;Kim, Sun-Hun;Kim, Min-Seok
    • International Journal of Oral Biology
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    • v.36 no.3
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    • pp.135-141
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    • 2011
  • Hertwig's epithelial root sheath (HERS) consists of bi-layered cells derived from the inner and outer dental epithelia and plays important roles in tooth root formation as well as in the maintenance and regeneration of periodontal tissues. With regards to the fate of HERS, and although previous reports have suggested that this entails the formation of epithelial rests of Malassez, apoptosis or an epithelial-mesenchymal transformation (EMT), it is unclear what changes occur in the epithelial cells in this structure. This study examined whether HERS cells undergo EMT using a keratin-14 (K14) cre:ROSA 26 transgenic reporter mouse. The K14 transgene is expressed by many epithelial tissues, including the oral epithelium and the enamel organ. A distinct K14 expression pattern was found in the continuous HERS bi-layer and the epithelial diaphragm were visualized by detecting the ${\beta}$-galactosidase (lacZ) activity in 1 week postnatal mice. The 2 and 4 week old mice showed a fragmented HERS with cell aggregation along the root surface. However, some of the lacZ-positive dissociated cells along the root surface were not positive for pan-cytokeratin. These results suggest that the K14 transgene is a valuable marker of HERS. In addition, the current data suggest that some of the HERS cells may lose their epithelial properties after fragmentation and subsequently undergo EMT.

Inhibition of p90RSK activation sensitizes triple-negative breast cancer cells to cisplatin by inhibiting proliferation, migration and EMT

  • Jin, Yujin;Huynh, Diem Thi Ngoc;Kang, Keon Wook;Myung, Chang-Seon;Heo, Kyung-Sun
    • BMB Reports
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    • v.52 no.12
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    • pp.706-711
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    • 2019
  • Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelial-mesenchymal transition (EMT) in breast cancer cells. First, we discovered that MDA-MB-231 cells exhibited more Cis-DDP resistance than other breast cancer cells, including MCF-7 and BT549 cells. Cis-DDP increased p90RSK activation, whereas the inactivation of p90RSK using a small interfering RNA (siRNA) or dominant-negative kinase mutant plasmid overexpression significantly reduced Cis-DDP-induced cell proliferation and migration via the inhibition of matrix metallopeptidase (MMP)2 and MMP9 in MDA-MB-231 cells. In addition, p90RSK activation was involved in EMT via the upregulation of mRNA expression, including that of Snail, Twist, ZEB1, N-cadherin, and vimentin. We also investigated NF-κB, the upstream regulator of EMT markers, and discovered that Cis-DDP treatment led to NF-κB translocation in the nucleus as well as its promoter activity. Our results suggest that targeting p90RSK would be a good strategy to increase Cis-DDP sensitivity in triple-negative breast cancers.

Korean Red Ginseng extract reduces hypoxia-induced epithelial-mesenchymal transition by repressing NF-κB and ERK1/2 pathways in colon cancer

  • Kim, Eui Joo;Kwon, Kwang An;Lee, Young Eun;Kim, Ju Hyun;Kim, Se-Hee;Kim, Jung Ho
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.288-297
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    • 2018
  • Background: The incidence of colorectal cancer (CRC) is increasing, with metastasis of newly diagnosed CRC reported in a large proportion of patients. However, the effect of Korean Red Ginseng extracts (KRGE) on epithelial to mesenchymal transition (EMT) in CRC is unknown. Therefore, we examined the mechanisms by which KRGE regulates EMT of CRC in hypoxic conditions. Methods: Human CRC cell lines HT29 and HCT116 were incubated under hypoxic (1% oxygen) and normoxic (21% oxygen) conditions. Western blot analysis and real-time PCR were used to evaluate the expression of EMT markers in the presence of KRGE. Furthermore, we performed scratched wound healing, transwell migration, and invasion assays to monitor whether KRGE affects migratory and invasive abilities of CRC cells under hypoxic conditions. Results: KRGE-treated HT29 and HCT116 cells displayed attenuated vascular endothelial growth factor (VEGF) mRNA levels and hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) protein expression under hypoxic conditions. KRGE repressed Snail, Slug, and Twist mRNA expression and integrin ${\alpha}V{\beta}6$ protein levels. Furthermore, hypoxia-repressed E-cadherin was restored in KRGE-treated cells; KRGE blocked the invasion and migration of colon cancer cells by repressing $NF-{\kappa}B$ and ERK1/2 pathways in hypoxia. Conclusions: KRGE inhibits hypoxia-induced EMT by repressing $NF-{\kappa}B$ and ERK1/2 pathways in colon cancer cells.

TP53I11 suppresses epithelial-mesenchymal transition and metastasis of breast cancer cells

  • Xiao, Tongqian;Xu, Zhongjuan;Zhang, Hai;Geng, Junsa;Qiao, Yong;Liang, Yu;Yu, Yanzhen;Dong, Qun;Suo, Guangli
    • BMB Reports
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    • v.52 no.6
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    • pp.379-384
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    • 2019
  • Epithelial-mesenchymal transition (EMT) is widely-considered to be a modulating factor of anoikis and cancer metastasis. We found that, in MDA-MB-231 cells, TP53I11 (tumor protein P53 inducible protein 11) suppressed EMT and migration in vitro, and inhibited metastasis in vivo. Our findings showed that hypoxic treatment upregulated the expression of $HIF1{\alpha}$, but reduced TP53I11 protein levels and TP53I11 overexpression reduced $HIF1{\alpha}$ expression under normal culture and hypoxicconditions, and in xenografts of MDA-MB-231 cells. Considering $HIF1{\alpha}$ is a master regulator of the hypoxic response and that hypoxia is a crucial trigger of cancer metastasis, our study suggests that TP53I11 may suppress EMT and metastasis by reducing $HIF1{\alpha}$ protein levels in breast cancer cells.

Factors associated with advanced airway management while performing cardiopulmonary resuscitation for out-of-hospital cardiac arrest patients by 119 EMT (병원 외 심정지 환자에서 119 구급대원의 전문기도유지술 시행에 영향을 미치는 요인)

  • Seo, Ah Ram;Kim, Dae Hee
    • The Korean Journal of Emergency Medical Services
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    • v.23 no.1
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    • pp.157-163
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    • 2019
  • Purpose: Advanced airway maintenance improves the quality of cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) patients. In this study, we evaluate the factors associated with advanced airway management while performing CPR for out-of-hospital cardiac arrest patients by 119 emergency medical technicians (EMTs). Methods: The observational analysis method was used ro retrospectively collect data from 119 rescue run sheets. This study was conducted in a fire station in Seoul, Korea. The subjects of this study were defined as OHCA patients who received CPR from July 2016 to June 2018. We divided the subjects into two groups according to whether advanced airway maintenance was performed or not, and then compared and analyzed both groups. We performed logistic regression analyses for characteristics that differed significantly between groups. Results: Out of 188 OHCA patients, 146 (77.7%) had received advanced airway management. Statistically significant differences in the logistic analysis were found regarding the total number of EMT professionals (adjusted odds ration [aOR]: 1.955; 95% confidence interval [CI]: 1.227-3.115; p=0.005) and scene-time (aOR:1.119;95%CI:1.019-1.228;p=0.019). Conclusion: Advanced airway maintenance while performing CPR for OHCA patients by EMT associated primarily with ensuring an adequate numbers of EMT professionals and sufficient scene time.

A Study of the Ethical Values of EMT students (응급구조과 학생의 윤리적 가치관에 관한 연구)

  • Kim, Mi-Seon
    • The Korean Journal of Emergency Medical Services
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    • v.5 no.1
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    • pp.37-51
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    • 2001
  • This study is aimed at examining the ethical values of EMT students. The results below are based on the revised questionnaires, which can be applicable to EMT from the original questionnaires developed by Lee(1990), with a sample of 124 students consisting of 63 first and 61 second year students, conducted November 2-8, 2001. Data were analyzed using SPSS in terms of means, standard deviations, t-test, ANOVA, Pearson's correlation coefficient. The results are as follows: 1. In the area of Human life, all subjects showed utilitarian disposition. All respondents perceived the item "When patients recognizing there is no hope for survival ask for euthanasia, it is ethically right to accommodate their opinions." as the most utilitarian item, whereas they perceived the item "When an hopeless patient is on cardiac arrest, it is ethically right to do CPR as the most deontoogical item. 2. In the area of patient relationship, all students of two groups took on deontoogical characteristics, but there were no statistically significant differences between two groups. All students perceived an item "EMT have to keep it secret if patients disclose their suicide intentions and ask for absolute secrecy" the most utilitarian item, whereas they perceived an item "Even though patients act and speak in a very rude manner, EMT people should do their best to provide care for patients." as the most deontoogical item. 3. In the area of task relationship, first year students perceived an item "Given time limitations, it is ethically right to give priority to the patients who can be rehabilitated over the patients who can't be fully recovered." as the most utilitarian item, whereas second year students perceived an item "Under no circumstances should any placebo be administered to patients." as the most utilitarian item. All students perceived an item "When EMT students see an unconscious person lying in the street, they have to give him/her emergency treatment." as the most deontoogical item. 4. In the area of coworker relationship, all students of two groups took on deontoogical disposition, but there were no significant differences between two groups. All students of two groups perceived an item "Suppose you are regarded as the person who would be promoted. However, you think that your coworker is more competent than you. In that case you should tell your supervisor about your coworker." as the most utilitarian item. First year students perceived an item, whereas second year students perceived an item "When you observe coworkers' misconduct at work, it is ethically right to ignore their misdeeds." as the most deontoogical item. 5. This study demonstrated that for the first year students, there is a correlational relationship between areas of human life and task relationship, and between areas of task relationship and coworker relationship, whereas for the second year students, there is a correlational relationship between areas of human life and task relationship. 6. In areas of human life and task relationship, there are significant differences according to attitudes toward EMT and attendance at ethics training sessions. In the area of coworker relationship, there are significant differences according to religion, attendance at ethics training sessions, and a code of ethics. Recommendations for future research, 1. Sample items to measure ethical values and the instrument tailored to the needs of EMT should be developed. 2. A longitudinal study to track ethical value changes according to the amount of work experience is needed. 3. A code of ethics and/or ethics training, which could apply in actual situations, should be implemented.

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Chloroquine Exerts Anti-metastatic Activities Under Hypoxic Conditions in Cholangiocarcinoma Cells

  • Thongchot, Suyanee;Loilome, Watcharin;Yongvanit, Puangrat;Dokduang, Hasaya;Thanan, Raynoo;Techasen, Anchalee;Namwat, Nisana
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2031-2035
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    • 2015
  • Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.